Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease.

BACKGROUND: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. METHODS: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. RESULTS: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. CONCLUSION: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

Minimal Clinically Important Differences and Feasibility of Dyspnea-12 and the Multidimensional Dyspnea Profile in Cardiorespiratory Disease.

CONTEXT: Breathlessness is a cardinal symptom in cardiorespiratory disease and consists of multiple dimensions that can be measured using the instruments Dyspnea-12 (D12) and the Multidimensional Dyspnea Profile (MDP). OBJECTIVES: The objective of the study is to determine the minimal clinically important differences (MCIDs) of all D12 and MDP summary and subdomain scores as well as the instruments' feasibility in patients with cardiorespiratory disease. METHODS: Prospective multicenter cohort study of outpatients with diagnosed cardiorespiratory disease and breathlessness in daily life. D12 and MDP were assessed at baseline, after 30-90 minutes and two weeks. MCIDs were calculated using anchor-based and distributional methods for summary and subdomain scores. Feasibility was assessed as rate of missing data, help required, self-reported difficulty, and completion time. RESULTS: A total 182 outpatients (53.3% women) were included; main diagnoses were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%), and idiopathic pulmonary fibrosis (19%). Anchor-based MCIDs were for D12 total score 2.83 (95% CI 1.99-3.66); D12 physical 1.81 (1.29-2.34); D12 affective 1.07 (0.64-1.49); MDP A1 unpleasantness 0.82 (0.56-1.08); MDP perception 4.63 (3.21-6.05), and MDP emotional score 2.37 (1.10-3.64). The estimates were consistent with small-to-moderate effect sizes using distributional analysis, and MCIDs were similar between COPD and non-COPD patients. The instruments were generally feasible and quick to use. CONCLUSION: D12 and MDP are responsive to change and feasible for use for assessing multidimensional breathlessness in outpatients with cardiorespiratory disease. MCIDs were determined for use as endpoints in clinical trials.

Feasibility of unconstrained three-material decomposition: imaging an excised human heart using a prototype silicon photon-counting CT detector.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of unconstrained three-material decomposition in a human tissue specimen containing iodinated contrast agent, using an experimental multi-bin photon-counting silicon detector. It was further to evaluate potential added clinical value compared to a 1st-generation state-of-the-art dual-energy computed tomography system. MATERIALS AND METHODS: A prototype photon-counting silicon detector in a bench-top setup for x-ray tomographic imaging was calibrated using a multi-material calibration phantom. A heart with calcified plaque was obtained from a deceased patient, and the coronary arteries were injected with an iodinated contrast agent mixed with gelatin. The heart was imaged in the experimental setup and on a 1st-generation state-of-the-art dual-energy computed tomography system. Projection-based three-material decomposition without any constraints was performed with the photon-counting detector data, and the resulting images were compared with those obtained from the dual-energy system. RESULTS: The photon-counting detector images show better separation of iodine and calcium compared to the dual-energy images. Additional experiments confirmed that unbiased estimates of soft tissue, calcium, and iodine could be achieved without any constraints. CONCLUSION: The proposed experimental system could provide added clinical value compared to current dual-energy systems for imaging tasks where mix-up of iodine and calcium is an issue, and the anatomy is sufficiently small to allow iodine to be differentiated from calcium. Considering its previously shown count rate capability, these results show promise for future integration of this detector in a clinical CT scanner. KEY POINTS: • Spectral photon-counting detectors can solve some of the fundamental problems with conventional single-energy CT. • Dual-energy methods can be used to differentiate iodine and calcium, but to do so must rely on constraints, since solving for three unknowns with only two measurements is not possible. Photon-counting detectors can improve upon these methods by allowing unconstrained three-material decomposition. • A prototype photon-counting silicon detector with high count rate capability allows performing unconstrained three-material decomposition and qualitatively shows better differentiation of iodine and calcium than dual-energy CT.

Erratum for "A Framework for Evaluating Threshold Variation Compensation Methods in Photon Counting Spectral CT".

On page 1862 of [1] (the second page of the article), in the second column, between (5) and (6), the current text "variations in the measured number of counts between different dels" should be replaced with "variations in the log normalized measured number of counts between different dels."

Validation of the Swedish Multidimensional Dyspnea Profile (MDP) in outpatients with cardiorespiratory disease.

Introduction: Breathlessness is a cardinal symptom in cardiorespiratory disease. An instrument for measuring different aspects of breathlessness was recently developed, the Multidimensional Dyspnea Profile (MDP). This study aimed to validate the MDP in terms of the underlying factor structure, internal consistency, test-retest reliability and concurrent validity in Swedish outpatients with cardiorespiratory disease. Methods: Outpatients with stable cardiorespiratory disease and breathlessness in daily life were recruited. Factor structure of MDP was analysed using confirmatory factor analysis; internal consistency was analysed using Cronbach's alpha; and test-retest reliability was analysed using intraclass correlation coefficients (ICCs) for patients with unchanged breathlessness between assessments (baseline, after 30-90 min and 2 weeks). Concurrent validity was evaluated using correlations with validated scales of breathlessness, anxiety, depression and health-related quality of life. Results: In total, 182 outpatients with cardiorespiratory disease and breathlessness in daily life were included; 53.3% were women; main diagnoses were chronic obstructive pulmonary disease (24.7%), asthma (21.4%), heart failure (19.2%) and idiopathic pulmonary fibrosis (18.7%). The MDP total, immediate perception and emotional response scores, and individual item scores showed expected factor structure and acceptable measurement properties: internal consistency (Cronbach's alpha, range 0.80-0.93); test-retest reliability at 30-90 min and 2 weeks (ICC, range 0.67-0.91); and concurrent validity. There was no evidence of a learning effect. Findings were similar between diagnoses. Discussion: MDP is a valid instrument for multidimensional measurement of breathlessness in Swedish outpatients across cardiorespiratory diseases.

Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease.

Introduction: Breathlessness is the cardinal symptom in both cardiac and respiratory diseases, and includes multiple dimensions. The multidimensional instrument Dyspnoea-12 has been developed to assess both physical and affective components of breathlessness. This study aimed to perform a clinical validation of the Swedish version of Dyspnoea-12 in outpatients with cardiorespiratory disease. Methods: Stable outpatients with cardiorespiratory disease and self-reported breathlessness in daily life were recruited from five Swedish centres. Assessments of Dyspnoea-12 were performed at baseline, after 30-90 min and after 2 weeks. Factor structure was tested using confirmatory factor analysis and internal consistency using Cronbach's alpha. Test-retest reliability was analysed using intraclass correlation coefficients (ICCs). Concurrent validity at baseline was evaluated by examining correlations with lung function and several instruments for the assessment of symptoms and health status. Results: In total, 182 patients were included: with the mean age of 69 years and 53% women. The main causes of breathlessness were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%) and idiopathic pulmonary fibrosis (19%). Factor analysis confirmed the expected underlying two-component structure with two subdomains. The Dyspnoea-12 total score, physical subdomain score and affective subdomain scores showed high internal consistency (Cronbach's alpha 0.94, 0.84 and 0.80, respectively) and acceptable reliability after 2 weeks (ICC total scores 0.81, 0.79 and 0.73). Dyspnoea-12 showed concurrent validity with the instruments modified Medical Research Council scale, COPD Assessment Test, European Quality of Life-Five Dimensions-Five levels, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and with forced expiratory volume in 1 s in percentage of predicted value. The results were consistent across different cardiorespiratory conditions. Conclusion: The Dyspnoea-12 is a valid instrument for multidimensional assessment of breathlessness in Swedish patients with cardiorespiratory diseases.

Subpixel x-ray imaging with an energy-resolving detector.

The detector pixel size can be a severe limitation in x-ray imaging of fine details in the human body. We demonstrate a method of using spectral x-ray measurements to image the spatial distribution of the linear attenuation coefficient on a length scale smaller than one pixel, based on the fact that interfaces parallel to the x-ray beam have a unique spectral response, which distinguishes them from homogeneous materials. We evaluate the method in a simulation study by simulating projection imaging of the border of an iodine insert with [Formula: see text] in a soft tissue phantom. The results show that the projected iodine profile can be recovered with an RMS resolution of 5% to 34% of the pixel size, using an ideal energy-resolving detector. We also validate this method in an experimental study by imaging an iodine insert in a polyethylene phantom using a photon-counting silicon-strip detector. The results show that abrupt and gradual transitions can be distinguished based on the transmitted x-ray spectrum, in good agreement with simulations. The demonstrated method may potentially be used for improving visualization of blood vessel boundaries, e.g., in acute stroke care.

Errata: Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications.

[This corrects the article DOI: 10.1117/1.JMI.2.3.033502.].

Upper limits of the photon fluence rate on CT detectors: Case study on a commercial scanner.

PURPOSE: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols. METHODS: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GE scanner [N. Keat, "CT scanner automatic exposure control systems," MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated. RESULTS: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ⋅ 10(8) mm(-2) s(-1), at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ⋅ 10(8) mm(-2) s(-1). The ECG gated chest protocol gives fluence rates up to 2.3 ⋅ 10(8) - 3.6 ⋅ 10(8) mm(-2) s(-1) depending on miscentering. CONCLUSIONS: The fluence rate on a CT detector reaches 3 ⋅ 10(8) - 6 ⋅ 10(8) mm(-2) s(-1) in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors.

Optimal frequency-based weighting for spectral x-ray projection imaging.

The purpose of this work is to derive a weighting scheme that maximizes the frequency-dependent ideal observer signal-difference-to-noise ratio, commonly referred to as detectability index or Hotelling-SDNR, for spectral X-ray projection imaging. Starting from basic statistical decision theory, optimal frequency-dependent weights are derived for a multiple-bin system and the Hotelling-SDNR calculated. A 28% increase in detectability index is found for high frequency objects when applying optimal frequency-dependent weights instead of pixel-based weights to a simplified model of a silicon detector, decreasing towards 0% for low frequency objects. Simulation results indicate a potentially large increase in detectability for high-frequency object imaging using silicon detectors, thus meriting further evaluations on a real system.

Allowable forward model misspecification for accurate basis decomposition in a silicon detector based spectral CT.

Material basis decomposition in the sinogram domain requires accurate knowledge of the forward model in spectral computed tomography (CT). Misspecifications over a certain limit will result in biased estimates and make quantum limited (where statistical noise dominates) quantitative CT difficult. We present a method whereby users can determine the degree of allowed misspecification error in a spectral CT forward model and still have quantification errors that are limited by the inherent statistical uncertainty. For a particular silicon detector based spectral CT system, we conclude that threshold determination is the most critical factor and that the bin edges need to be known to within 0.15 keV in order to be able to perform quantum limited material basis decomposition. The method as such is general to all multibin systems.

Theoretical comparison of a dual energy system and photon counting silicon detector used for material quantification in spectral CT.

Any method using dual energy computed tomography (CT) has to make prior assumptions in order to quantify k-edge contrast agents. This work estimates the mean square error (MSE) in contrast agent quantification employing a method based on assigning each reconstructed voxel a ratio of soft tissue and fat using dual energy CT. The results are compared to the MSE using a photon counting silicon detector with multiple bins. The square root of the MSEs of the quantifications of iodine and gadolinium for an object consisting of soft tissue and fat using the silicon detector and dual energy CT range from below 2% and 1% of the contrast agent content for 100 mg/cm(3) of iodine and gadolinium, up to approximately 10% and 13%, and 6% and 4%, for 5 mg/cm(3) of iodine and gadolinium, respectively. When adding bone with a voxel volume fraction of 2.2%, the square root of the MSEs of the quantifications of iodine and gadolinium using dual energy CT increases to 25% and 6%, respectively, for 5 mg/cm(3) of contrast agent. In conclusion, results indicate that the noise levels of the material quantification using the silicon detector are higher than the noise levels using a dual energy CT when the composition of the object is known. However, using a dual energy CT increases the risk of model specification error and subsequently a large bias in contrast agent quantification, a problem which does not exist when using a multi-bin CT where the number of energy bins is larger than two.

Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications.

Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy.

Energy-resolved CT imaging with a photon-counting silicon-strip detector.

Photon-counting detectors are promising candidates for use in the next generation of x-ray computed tomography (CT) scanners. Among the foreseen benefits are higher spatial resolution, better trade-off between noise and dose and energy discriminating capabilities. Silicon is an attractive detector material because of its low cost, mature manufacturing process and high hole mobility. However, it is sometimes overlooked for CT applications because of its low absorption efficiency and high fraction of Compton scatter. The purpose of this work is to demonstrate that silicon is a feasible material for CT detectors by showing energy-resolved CT images acquired with an 80 kVp x-ray tube spectrum using a photon-counting silicon-strip detector with eight energy thresholds developed in our group. We use a single detector module, consisting of a linear array of 50 0.5×0.4 mm detector elements, to image a phantom in a table-top lab setup. The phantom consists of a plastic cylinder with circular inserts containing water, fat and aqueous solutions of calcium, iodine and gadolinium, in different concentrations. By using basis material decomposition we obtain water, calcium, iodine and gadolinium basis images and demonstrate that these basis images can be used to separate the different materials in the inserts. We also show results showing that the detector has potential for quantitative measurements of substance concentrations.

Theoretical comparison of the iodine quantification accuracy of two spectral CT technologies.

We compare the theoretical limits of iodine quantification for the photon counting multibin and dual energy technologies. Dual energy systems by necessity have to make prior assumptions in order to quantify iodine. We explicitly allow the multibin system to make the same assumptions and also allow them to be wrong. We isolate the effect of technology from imperfections and implementation issues by assuming both technologies to be ideal, i.e., without scattered radiation, unity detection efficiency and perfect energy response functions, and by applying the Cramér-Rao lower bound methodology to assess the quantification accuracy. When priors are wrong the maximum likelihood estimates will be biased and the mean square error of the quantification error is a more appropriate figure of merit. The evaluation assumes identical X-ray spectra for both methodologies and for that reason a sensitivity analysis is performed with regard to the assumed X-ray spectrum. We show that when iodine is quantified over regions of interest larger than 6 cm(2), multibin systems benefit by independent estimation of three basis functions. For smaller regions of interest multibin systems can increase quantification accuracy by making the same prior assumptions as dual energy systems.

Eliminated risk of iodine contrast cancellation with multibin spectral CT.

This note compares the extent of contrast cancellation induced by iodinated contrast agents in energy integrating and photon counting multibin CT images. The contrast between a hypodense target and soft tissue is modeled for the two systems for a range of iodine concentrations and tube voltages. In energy integrating systems, we show that the contrast vanishes for low concentrations of iodine whereas the same effect is not seen in multibin systems. We conclude that it is the ability of multibin systems to apply weighting schemes post-acquisition that allows the operator to eliminate the risk of contrast cancellation between iodinated targets and the background.

A framework for evaluating threshold variation compensation methods in photon counting spectral CT.

One of the challenges in the development of photon counting spectral computed tomography (CT) detectors is that the location of the energy thresholds tends to vary among detector elements. If not compensated for, this threshold variation leads to ring artifacts in the reconstructed images. In this paper, a framework is presented for the systematic comparison of different methods of compensating for inhomogeneities among detector elements in photon counting CT with multiple energy bins. Furthermore, we propose the use of an affine minimum mean square error estimator, calibrated against transmission measurements on different combinations of two materials, for inhomogeneity compensation. Using the framework developed here, this method is compared to two other compensation schemes, flatfielding using an air scan and signal-to-thickness calibration using a step wedge calibrator, in a simulation study. The results show that for all but the lowest studied level of threshold spread, the proposed method is superior to signal-to-thickness calibration, which in turn is superior to flatfielding. We also demonstrate that the effects of threshold variation can be countered to a large extent by substructuring each detector element into depth segments.

Performance evaluation of a sub-millimetre spectrally resolved CT system on high- and low-frequency imaging tasks: a simulation.

We are developing a photon-counting silicon strip detector with 0.4 × 0.5 mm² detector elements for clinical CT applications. Except for the limited detection efficiency of approximately 0.8 for a spectrum of 80 kVp, the largest discrepancies from ideal spectral behaviour have been shown to be Compton interactions in the detector and electronic noise. Using the framework of cascaded system analysis, we reconstruct the 3D MTF and NPS of a silicon strip detector including the influence of scatter and charge sharing inside the detector. We compare the reconstructed noise and signal characteristics with a reconstructed 3D MTF and NPS of an ideal energy-integrating detector system with unity detection efficiency, no scatter or charge sharing inside the detector, unity presampling MTF and 1 × 1 mm² detector elements. The comparison is done by calculating the dose-normalized detectability index for some clinically relevant imaging tasks and spectra. This work demonstrates that although the detection efficiency of the silicon detector rapidly drops for the acceleration voltages encountered in clinical computed tomography practice, and despite the high fraction of Compton interactions due to the low atomic number, silicon detectors can perform on a par with ideal energy-integrating detectors for routine imaging tasks containing low-frequency components. For imaging tasks containing high-frequency components, the proposed silicon detector system can perform approximately 1.1-1.3 times better than a fully ideal energy-integrating system.

Synthetic Hounsfield units from spectral CT data.

Beam-hardening-free synthetic images with absolute CT numbers that radiologists are used to can be constructed from spectral CT data by forming 'dichromatic" images after basis decomposition. The CT numbers are accurate for all tissues and the method does not require additional reconstruction. This method prevents radiologists from having to relearn new rules-of-thumb regarding absolute CT numbers for various organs and conditions as conventional CT is replaced by spectral CT. Displaying the synthetic Hounsfield unit images side-by-side with images reconstructed for optimal detectability for a certain task can ease the transition from conventional to spectral CT.